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Redistribution of macrophage cholesteryl ester hydrolase from cytoplasm to lipid droplets upon lipid loading

Zhao, Bin, Fisher, Bernard J., Clair, Richard W. St., Rudel, Lawrence L., Ghosh, Shobha·2005·Journal of Lipid Research
DOI 10.1194/jlr.m500207-jlr200
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Abstract

Hydrolysis of intracellular cholesteryl esters (CEs) represents the first step in the removal of cholesterol from lipid-laden foam cells associated with atherosclerotic lesions. Neutral cholesteryl ester hydrolase (CEH) catalyzes this reaction, and we recently cloned the cDNA for the human macrophage CEH and demonstrated increased mobilization of intracellular CE droplets by CEH overexpression. The present study was undertaken to test the hypothesis that for CE hydrolysis, CEH must become associated with the surface of the cytoplasmic lipid droplets. Our data show the redistribution of CEH from cytosol to lipid droplets upon lipid loading of human THP-1 macrophages. Depletion of triacylglycerol (TG) by incubation with the acyl-CoA synthetase inhibitor Triacsin D had no effect on CEH association with the lipid droplets, suggesting that CEH associates with mixed (CE + TG) as well as TG-depleted CE droplets. However, CEH had 2.5-fold higher activity when mixed droplets were used as substrate in an in vitro assay, consistent with the reported higher cholesterol efflux from cells containing mixed isotropic droplets. Perilipin as well as adipophilin, two lipid droplet-associated proteins, were also present on the lipid droplets in THP-1 macrophages. In conclusion, CEH associates with its intracellular substrate (lipid droplets) and hydrolyzes CE more efficiently from mixed droplets.

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Crossref · 10.1194/jlr.m500207-jlr200

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  • The endocytic recycling compartment (ERC) is a major sterol storage organelle and an important station for cholesterol in the endocytic pathway.

    “the tubulo-vesicular endocytic recycling compartment [9,10], which has also been defined as a major sterol storage organelle [11]”

    From EHD1 regulates cholesterol homeostasis and lipid droplet storage (2007) · cites this paper as [11]

  • A dominant-negative EHD1 mutant (G429R) delays recycling of transferrin and dehydroergosterol in CHO cells.

    “studies in CHO cells using a ‘dominant-negative’ EHD1 mutant (G429R) have demonstrated delays in the recycling of both transferrin and dehydroergosterol, a naturally occurring sterol with a chemical structure highly similar to cholesterol [11].”

    From EHD1 regulates cholesterol homeostasis and lipid droplet storage (2007) · cites this paper as [11]

Citations

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Research works printed but not linked: 29

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Metadata

Authors
Zhao, B., Fisher, B. J., Clair, R. W. S., Rudel, L. L., & Ghosh, S.
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2005-10
Volume
46
Issue
10
Pages
2114-2121
ISSN
0022-2275
DOI
10.1194/jlr.m500207-jlr200
Cited by
51
References
0
Language
en
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